Cargando…
Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli
The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) inductio...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772759/ https://www.ncbi.nlm.nih.gov/pubmed/35052944 http://dx.doi.org/10.3390/antibiotics11010067 |
_version_ | 1784635918569701376 |
---|---|
author | Mallik, Dhriti Jain, Diamond Bhakta, Sanjib Ghosh, Anindya Sundar |
author_facet | Mallik, Dhriti Jain, Diamond Bhakta, Sanjib Ghosh, Anindya Sundar |
author_sort | Mallik, Dhriti |
collection | PubMed |
description | The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (ampD, ampE and ampG) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆ampD and ∆ampE mutants of E. coli, we attempted to elucidate the effects of ampD and ampE on the expression of serine-BLAs originating from Enterobacteriaceae, viz., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆ampD and ∆ampE mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon in trans expression of ampD, whereas the same is decreased upon ampE expression, indicating a differential effect of ampD and ampE overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA. |
format | Online Article Text |
id | pubmed-8772759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87727592022-01-21 Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli Mallik, Dhriti Jain, Diamond Bhakta, Sanjib Ghosh, Anindya Sundar Antibiotics (Basel) Article The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (ampD, ampE and ampG) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆ampD and ∆ampE mutants of E. coli, we attempted to elucidate the effects of ampD and ampE on the expression of serine-BLAs originating from Enterobacteriaceae, viz., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆ampD and ∆ampE mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon in trans expression of ampD, whereas the same is decreased upon ampE expression, indicating a differential effect of ampD and ampE overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA. MDPI 2022-01-06 /pmc/articles/PMC8772759/ /pubmed/35052944 http://dx.doi.org/10.3390/antibiotics11010067 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mallik, Dhriti Jain, Diamond Bhakta, Sanjib Ghosh, Anindya Sundar Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli |
title | Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli |
title_full | Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli |
title_fullStr | Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli |
title_full_unstemmed | Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli |
title_short | Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli |
title_sort | role of ampc-inducing genes in modulating other serine beta-lactamases in escherichia coli |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772759/ https://www.ncbi.nlm.nih.gov/pubmed/35052944 http://dx.doi.org/10.3390/antibiotics11010067 |
work_keys_str_mv | AT mallikdhriti roleofampcinducinggenesinmodulatingotherserinebetalactamasesinescherichiacoli AT jaindiamond roleofampcinducinggenesinmodulatingotherserinebetalactamasesinescherichiacoli AT bhaktasanjib roleofampcinducinggenesinmodulatingotherserinebetalactamasesinescherichiacoli AT ghoshanindyasundar roleofampcinducinggenesinmodulatingotherserinebetalactamasesinescherichiacoli |